Вплив ліпосомальної трансфекції клітин головного мозку геном апоЕ3 на пошкодження аксонів, зумовлене експериментальною черепно-мозковою травмою

Vadym Biloshytsky; Sergey Mikhalsky; Tatyana Kvitnitskaya-Ryzhova

doi:10.25305/unj.57795

Authors

Vadym Biloshytsky Romodanov Neurosurgery Institute, Kiev, Ukraine
Sergey Mikhalsky D.F.Chebotarev State Institute of Gerontology, Kiev, Ukraine
Tatyana Kvitnitskaya-Ryzhova D.F.Chebotarev State Institute of Gerontology, Kiev, Ukraine

DOI:

https://doi.org/10.25305/unj.57795

Keywords:

traumatic brain injury, gene therapy, apolipoprotein E, diffuse axonal injury

Abstract

The goal of study was to estimate the structural damage of axons in rats with severe traumatic brain injury (TBI), and the possibilities of such disorders correction by means of gene therapy that launches the synthesis of e3 isoform of apolipoprotein E in brain tissue. Severe diffuse TBI in rats was inflicted under overall anesthesia by free load weighing 450 g, falling from a 1.5 m elevation. The mixture of DOTAP liposome and 25 µg of plasmid vector pCMV•SPORT6 with cDNA of APOE3 gene was infused intraventricularly using ALZET osmotic pumps. Severe experimental TBI is characterized by the damage of hippocampal cytoarchitectonics with destructive-dystrophic changes of all brain elements (neurons, glia, capillaries). The distinguishing feature of this damage is diffuse axonal injury exhibited by pronounced changes of axonal cytoskeleton, axonal edema and deformity, mitochondrial destruction and serious damage to myelin sheathes. The liposome-mediated brain tissue transfection with plasmid vector carrying the gene of e3 isoform of apolipoprotein E has a positive therapeutic effect after TBI including the decrease of diffuse axonal injury.

References

Clinical trials in head injury / R.K. Narayan, M.E. Michel, B. Ansell [et al.] // J. Neurotrauma. — 2002. — V.19,N5. — P.503–557.

Johnston A.J. Advanced monitoring in the neurology intensive care unit: microdialysis / A.J. Johnston, A.K.Gupta // Curr. Opin. Crit. Care. — 2002. — V.8, N2. — P.121–127.

Maxwell W.L. A mechanistic analysis of nondisruptive axonal injury: a review / W.L. Maxwell, J.T. Povlishock, D.L. Graham // J. Neurotrauma. — 1997. — V.14. — P.419–440.

Park E. Traumatic brain injury: Can the consequences be stopped? / E. Park, J.D. Bell // C.M.A.J. — 2008. — V.178, N9. — P.1163–1170.

Wang H.-C. Experimental models of traumatic axonal injury / H.-C. Wang, Y.-B. Ma // J. Clin. Neurosci. — 2010. — V.17. —P.157–162.

Влияние трансфекции гена аполипопротеина Е человека на структуру гиппокампа и когнитивные нарушения после черепно-мозговой травмы у крыс разного возраста / С.А. Михальский, В.В. Белошицкий, Л.А. Цыба [и др.] // Пробл. старения и долголетия. — 2008. — Т.17, №2. — С.240–258.

Влияние липосомальной трансфекции гена аполипопротеина Е3 на динамику неврологического и когнитивного дефицита при черепно-мозговой травме в эксперименте / В.В. Белошицкий, Н.Я. Гридина, Цыба Л.А., Величко О.Н. // Укр. нейрохірург. журн. — 2009. — №2. — С. 59–60.

Вплив ліпосомальної трансфекції в клітини головного мозку гену апоЕ3 на дослідницьку поведінку та емоційний стан щурів після експериментальної черепно-мозкової травми / В.В. Білошицький, О.М. Величко, Н.Я. Гридіна [та ін.] // Укр. нейрохірург. журн. — 2010. — №2. — С.55–62.

Acute subdural hematoma and diffuse axonal injury after severe head trauma / J. Sahuquillo-Barris, J. Lamarca-Ciuro, J. Vilalta-Castan [et al.] // J. Neurosurg. — 1988. — V.68. — P.894–900.

Axonal injury: a universal consequence of fatal closed head injury? / S.M. Gentleman, G.W. Roberts, T.A. Gennarelli [et al.] // Acta Neuropathol. (Berl.). — 1995. — V.89. — P.537–543.

Reinert M.M. Clinical trials in head injury / M.M. Reinert, R. Bullock // Neurol. Res. — 1999. — V.21. — P.330–338.

Immediate coma following inertial brain injury dependent on axonal damage in the brainstem / D.H. Smith, M. Nonaka, R. Miller [et al.] // J. Neurosurg. — 2000. — V.93. — P.315–322.

Ultrastructural evidence of axonal shearing as a result of lateral acceleration of the head in non-human primates / W.L. Maxwell, C. Watt, D.I. Graham [et al.] // Acta Neuropathol. (Berl.). — 1993. — V.86. — P.136–144.

Traumatic axonal injury induces calcium influx modulated by tetrodotoxin-sensitive sodium channels / J.A. Wolf, P.K. Stys, T. Lusardi [et al.] // J. Neurosci. — 2001. — V.21. — P.1923–1930.

Buki A. All roads lead to disconnection? Traumatic axonal injury revisited / A. Buki, J.T. Povlishock // Acta Neurochir. (Wien). — 2006. — V.148. — P.181–194.

Toxic proteins released from mitochondria in cell death / X. Saelens, N. Festjens, L. Vande Walle [et al.] // Oncogene. — 2004. — V.23. — P.2861–2874.

The role of calpain-mediated spectrin proteolysis in traumatically induced axonal injury / A. Buki, R. Siman, J.Q. Trojanowski, J.T. Povlishock // J. Neuropathol. Exp. Neurol. — 1999. — V.58. — P.365–375.

Apoptotic and antiapoptotic mechanisms after traumatic brain injury / R.W. Keane, S. Kraydieh, G. Lotocki [et al.] // J. Cereb. Blood Flow Metab. — 2001. — V.21, N10. — P.1189–1198.

Apolipoprotein E-genotype dependent hippocampal and cortical responses to traumatic brain injury / F. Crawford, M. Wood,S. Ferguson[et al.] // Neuroscience. — 2009. — V.159. — P.1349–1362.

Apolipoprotein E-containing lipoproteins protect neurons from apoptosis via a signaling pathway involving low-density lipoprotein receptor-related protein-1 / H. Hayashi, R. B. Campenot, D.E. Vance, J.E. Vance // J. Neurosci. — 2007. — V.27, N8. — P.1933–1941.